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Zanubrutinib (BGB-3111) in Participants With Previously Treated B-Cell Lymphoma Intolerant of Prior Bruton Tyrosine Kinase Inhibitor (BTKi) Treatment

Primary Purpose

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Zanubrutinib
Sponsored by
BeiGene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma focused on measuring BGB-3111, Zanubrutinib, Ibrutinib Intolerance, BTK Inhibitor, Acalabrutinib Intolerance

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  1. Participants must meet protocol defined disease criteria requiring treatment for their respective disease prior to initiation of ibrutinib or acalabrutinib
  2. Ibrutinib and acalabrutinib intolerance is defined as an unacceptable toxicity where, in the opinion of the investigator, treatment should be discontinued in spite of optimal supportive care as a result of one of the following:

    1. For ibrutinib and acalabrutinib intolerance events:

      • 1 or more ≥ Grade 2 nonhematologic toxicities for >7 days (with or without treatment)
      • 1 or more ≥ Grade 3 nonhematologic toxicity of any duration
      • 1 or more Grade 3 neutropenia with infection or fever of any duration; or
      • Grade 4 heme toxicity which persists to the point that the investigator chose to stop therapy due to toxicity NOT progression.
    2. For acalabrutinib intolerance events only;

      • 1 or more ≥ Grade 1 nonhematologic toxicities of any duration with > 3 recurrent episodes; or
      • 1 or more ≥ Grade 1 nonhematologic toxicities for > 7 days (with or without treatment); or
      • Inability to use acid-reducing agents or anticoagulants (eg, proton pump inhibitors, warfarin) due to concurrent acalabrutinib use
  3. Ibrutinib and/or acalabrutinib-related ≥ Grade 2 toxicities must have resolved to ≤ Grade 1 or baseline prior to initiating treatment with zanubrutinib. Grade 1 acalabrutinib-related toxicities must have resolved to Grade 0 or baseline prior to initiating treatment with zanubrutinib.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  5. Absolute neutrophil count (ANC) ≥ 1000/mm^3 with or without growth factor support and platelet count ≥ 50,000/mm^3 (may be post-transfusion), on or prior to C1D1 of zanubrutinib

Key Exclusion Criteria:

  1. Clinically significant cardiovascular disease including the following:

    1. Myocardial infarction within 6 months before the Screening
    2. Unstable angina within 3 months before the Screening
    3. New York Heart Association class III or IV congestive heart failure
    4. History of sustained ventricular tachycardia, ventricular fibrillation, and/or Torsades de Pointes
    5. QT interval corrected by Fridericia's formula > 480 milliseconds
    6. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
  2. History of central nervous system (CNS) hemorrhage
  3. Documented progressive disease (PD) during ibrutinib and/or acalabrutinib treatment.
  4. Have received any anticancer therapy (other than immunotherapy) for CLL/SLL, WM, MCL, and MZL < 7 days before any Screening assessments are performed or any immunotherapy treatment, taken alone or as part of a chemoimmunotherapy regimen, < 4 weeks before any Screening assessments are performed
  5. Requires ongoing need for corticosteroid treatment > 10 mg daily of prednisone or equivalent corticosteroid. Note: Systemic corticosteroids must be fully tapered off/discontinued ≥ 5 days before the first dose of study drug is administered.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Sites / Locations

  • Arizona Oncology Associates, Pc HopeRecruiting
  • Rocky Mountain Cancer Centers (Williams) UsorRecruiting
  • Christiana CareRecruiting
  • Scri Florida Cancer Specialists SouthRecruiting
  • St Century OncologyRecruiting
  • Scri Florida Cancer Specialists NorthRecruiting
  • Healthcare Research Network Iii, LlcRecruiting
  • Minnesota Oncology Burnsville ClinicRecruiting
  • Comprehensive Cancer Centers of NevadaRecruiting
  • Summit Medical GroupRecruiting
  • Morristown Medical CenterRecruiting
  • Clinical Research Alliance, IncRecruiting
  • Oncology Associates of Oregon Willamette Valley Cancer CenterRecruiting
  • St Lukes University Health NetworkRecruiting
  • Abington Hematology Oncology AssociatesRecruiting
  • Tennessee Oncology, Pllc NashvilleRecruiting
  • Texas Oncology AmarilloRecruiting
  • Baylor Research InstituteRecruiting
  • Texas Oncology McAllen South Second StreetRecruiting
  • Texas Oncology Tyler LongviewRecruiting
  • Us Oncology Virginia Cancer Specialists, PcRecruiting
  • Fred Hutchinson Cancer Research CenterRecruiting
  • Medical Oncology AssociatesRecruiting
  • Ssm Health Cancer Care Dean Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zanubrutinib

Arm Description

Cohort 1: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) previously treated with ibrutinib Cohort 2: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) previously treated with acalabrutinib alone/with ibrutinib

Outcomes

Primary Outcome Measures

Recurrence and change in severity of treatment-emergent Adverse Events (AEs) of interest.

Secondary Outcome Measures

Overall response as determined by investigator
Progression free survival (PFS) as determined by investigator
Patient reported outcomes as measured by EuroQol five dimension scale (EQ-5D)
Patient reported outcomes as measured by European Organisation for Research and Treatment of Cancer (EORTC)
Disease control rate as determined by investigator

Full Information

First Posted
October 1, 2019
Last Updated
July 17, 2023
Sponsor
BeiGene
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1. Study Identification

Unique Protocol Identification Number
NCT04116437
Brief Title
Zanubrutinib (BGB-3111) in Participants With Previously Treated B-Cell Lymphoma Intolerant of Prior Bruton Tyrosine Kinase Inhibitor (BTKi) Treatment
Official Title
A Phase 2, Multicenter, Single-arm Study of Zanubrutinib (BGB-3111) in Patients With Previously Treated B-Cell Lymphoma Intolerant of Prior Treatment With Ibrutinib and/or Acalabrutinib
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 15, 2019 (Actual)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BeiGene

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective of this study is to evaluate the safety of zanubrutinib (also known as BGB-3111) in chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström macroglobulinemia, mantle cell lymphoma, or marginal zone lymphoma patients who have become intolerant of prior ibrutinib and/or acalabrutinib treatment, by comparing intolerance to adverse event profile as assessed by the recurrence and the change in severity of adverse events.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Waldenstrom Macroglobulinemia
Keywords
BGB-3111, Zanubrutinib, Ibrutinib Intolerance, BTK Inhibitor, Acalabrutinib Intolerance

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Zanubrutinib
Arm Type
Experimental
Arm Description
Cohort 1: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) previously treated with ibrutinib Cohort 2: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) previously treated with acalabrutinib alone/with ibrutinib
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib
Other Intervention Name(s)
BGB-3111, BRUKINSA
Intervention Description
Zanubrutinib (BGB-3111) will be orally administered at a dose of 160 mg twice daily or 320mg once daily until disease progression, unacceptable toxicity, treatment consent withdrawal, or study termination.
Primary Outcome Measure Information:
Title
Recurrence and change in severity of treatment-emergent Adverse Events (AEs) of interest.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Overall response as determined by investigator
Time Frame
24 months
Title
Progression free survival (PFS) as determined by investigator
Time Frame
24 months
Title
Patient reported outcomes as measured by EuroQol five dimension scale (EQ-5D)
Time Frame
24 months
Title
Patient reported outcomes as measured by European Organisation for Research and Treatment of Cancer (EORTC)
Time Frame
24 months
Title
Disease control rate as determined by investigator
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Participants must meet protocol defined disease criteria requiring treatment for their respective disease prior to initiation of ibrutinib or acalabrutinib Ibrutinib and acalabrutinib intolerance is defined as an unacceptable toxicity where, in the opinion of the investigator, treatment should be discontinued in spite of optimal supportive care as a result of one of the following: For ibrutinib and acalabrutinib intolerance events: 1 or more ≥ Grade 2 nonhematologic toxicities for >7 days (with or without treatment) 1 or more ≥ Grade 3 nonhematologic toxicity of any duration 1 or more Grade 3 neutropenia with infection or fever of any duration; or Grade 4 heme toxicity which persists to the point that the investigator chose to stop therapy due to toxicity NOT progression. For acalabrutinib intolerance events only; 1 or more ≥ Grade 1 nonhematologic toxicities of any duration with > 3 recurrent episodes; or 1 or more ≥ Grade 1 nonhematologic toxicities for > 7 days (with or without treatment); or Inability to use acid-reducing agents or anticoagulants (eg, proton pump inhibitors, warfarin) due to concurrent acalabrutinib use Ibrutinib and/or acalabrutinib-related ≥ Grade 2 toxicities must have resolved to ≤ Grade 1 or baseline prior to initiating treatment with zanubrutinib. Grade 1 acalabrutinib-related toxicities must have resolved to Grade 0 or baseline prior to initiating treatment with zanubrutinib. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Absolute neutrophil count (ANC) ≥ 1000/mm^3 with or without growth factor support and platelet count ≥ 50,000/mm^3 (may be post-transfusion), on or prior to C1D1 of zanubrutinib Key Exclusion Criteria: Clinically significant cardiovascular disease including the following: Myocardial infarction within 6 months before the Screening Unstable angina within 3 months before the Screening New York Heart Association class III or IV congestive heart failure History of sustained ventricular tachycardia, ventricular fibrillation, and/or Torsades de Pointes QT interval corrected by Fridericia's formula > 480 milliseconds History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place History of central nervous system (CNS) hemorrhage Documented progressive disease (PD) during ibrutinib and/or acalabrutinib treatment. Have received any anticancer therapy (other than immunotherapy) for CLL/SLL, WM, MCL, and MZL < 7 days before any Screening assessments are performed or any immunotherapy treatment, taken alone or as part of a chemoimmunotherapy regimen, < 4 weeks before any Screening assessments are performed Requires ongoing need for corticosteroid treatment > 10 mg daily of prednisone or equivalent corticosteroid. Note: Systemic corticosteroids must be fully tapered off/discontinued ≥ 5 days before the first dose of study drug is administered. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
BeiGene
Phone
1-877-828-5568
Email
clinicaltrials@beigene.com
Facility Information:
Facility Name
Arizona Oncology Associates, Pc Hope
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85711
Country
United States
Individual Site Status
Recruiting
Facility Name
Rocky Mountain Cancer Centers (Williams) Usor
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80012
Country
United States
Individual Site Status
Recruiting
Facility Name
Christiana Care
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Individual Site Status
Recruiting
Facility Name
Scri Florida Cancer Specialists South
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33901
Country
United States
Individual Site Status
Recruiting
Facility Name
St Century Oncology
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32204
Country
United States
Individual Site Status
Recruiting
Facility Name
Scri Florida Cancer Specialists North
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33705
Country
United States
Individual Site Status
Recruiting
Facility Name
Healthcare Research Network Iii, Llc
City
Tinley Park
State/Province
Illinois
ZIP/Postal Code
60487
Country
United States
Individual Site Status
Recruiting
Facility Name
Minnesota Oncology Burnsville Clinic
City
Burnsville
State/Province
Minnesota
ZIP/Postal Code
55337
Country
United States
Individual Site Status
Recruiting
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Individual Site Status
Recruiting
Facility Name
Summit Medical Group
City
Florham Park
State/Province
New Jersey
ZIP/Postal Code
07932
Country
United States
Individual Site Status
Recruiting
Facility Name
Morristown Medical Center
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07960
Country
United States
Individual Site Status
Recruiting
Facility Name
Clinical Research Alliance, Inc
City
Westbury
State/Province
New York
ZIP/Postal Code
11590
Country
United States
Individual Site Status
Recruiting
Facility Name
Oncology Associates of Oregon Willamette Valley Cancer Center
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Individual Site Status
Recruiting
Facility Name
St Lukes University Health Network
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18015
Country
United States
Individual Site Status
Recruiting
Facility Name
Abington Hematology Oncology Associates
City
Horsham
State/Province
Pennsylvania
ZIP/Postal Code
19044
Country
United States
Individual Site Status
Recruiting
Facility Name
Tennessee Oncology, Pllc Nashville
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Name
Texas Oncology Amarillo
City
Amarillo
State/Province
Texas
ZIP/Postal Code
79106
Country
United States
Individual Site Status
Recruiting
Facility Name
Baylor Research Institute
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Individual Site Status
Recruiting
Facility Name
Texas Oncology McAllen South Second Street
City
McAllen
State/Province
Texas
ZIP/Postal Code
78503
Country
United States
Individual Site Status
Recruiting
Facility Name
Texas Oncology Tyler Longview
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Individual Site Status
Recruiting
Facility Name
Us Oncology Virginia Cancer Specialists, Pc
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Recruiting
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Name
Medical Oncology Associates
City
Spokane
State/Province
Washington
ZIP/Postal Code
99208
Country
United States
Individual Site Status
Recruiting
Facility Name
Ssm Health Cancer Care Dean Medical Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53717
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
36400069
Citation
Shadman M, Flinn IW, Levy MY, Porter RF, Burke JM, Zafar SF, Misleh J, Kingsley EC, Yimer HA, Freeman B, Rao SS, Chaudhry A, Tumula PK, Gandhi MD, Manda S, Chen DY, By K, Xu L, Liu Y, Crescenzo R, Idoine A, Zhang X, Cohen A, Huang J, Sharman JP. Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: a phase 2, open-label, single-arm study. Lancet Haematol. 2023 Jan;10(1):e35-e45. doi: 10.1016/S2352-3026(22)00320-9. Epub 2022 Nov 16.
Results Reference
derived

Learn more about this trial

Zanubrutinib (BGB-3111) in Participants With Previously Treated B-Cell Lymphoma Intolerant of Prior Bruton Tyrosine Kinase Inhibitor (BTKi) Treatment

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